ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.556C>T (p.Gln186Ter)

gnomAD frequency: 0.00001  dbSNP: rs1384677442
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001004340 SCV001163267 likely pathogenic Usher syndrome type 1 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV002549240 SCV003761090 likely pathogenic Usher syndrome type 1F 2023-01-24 criteria provided, single submitter curation The p.Gln186Ter variant in PCDH15 has been reported in 1 individual with Usher syndrome type 1F (PMID: 33576794) and has been identified in 0.09% (1/1088) of other chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1384677442). This variant has also been reported in ClinVar (Variation ID#: 813417) and has been interpreted as likely pathogenic by Baylor Genetics. This nonsense variant leads to a premature termination codon at position 186, which is predicted to lead to a truncated or absent protein. Loss of function of the PCDH15 gene is an established disease mechanism in autosomal recessive Usher syndrome type 1F. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive Usher syndrome type 1F. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015).
Baylor Genetics RCV003473548 SCV004200802 likely pathogenic Autosomal recessive nonsyndromic hearing loss 23 2024-03-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003769404 SCV004641411 pathogenic not provided 2024-02-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln186*) in the PCDH15 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCDH15 are known to be pathogenic (PMID: 11398101, 11487575, 14570705). This variant is present in population databases (no rsID available, gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Usher Syndrome (PMID: 33576794). ClinVar contains an entry for this variant (Variation ID: 813417). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005047193 SCV005677223 likely pathogenic Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F 2024-04-23 criteria provided, single submitter clinical testing

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